Old Horse Immune Function: Is Gene Length Key?

Is it possible genes that become shorter as horses age could be the key to how well that animal's immune system works?

The availability of horses 20 years old and older on the University of Kentucky's Maine Chance Farm and on farms in the Lexington area was one of the things that interested David Horohov, PhD, William Robert Mills Chair in Equine Immunology, when he joined the faculty at the Gluck Equine Research Center in 2003.

His interest in older horses was a continuation of work that he began 19 years ago while at Louisiana State University (LSU). That early interest grew from a collaborative research project involving researchers at Rutgers, The State University of New Jersey, led by Karyn Malinowski, PhD. That study focused on the effect of exercise on young and old Standardbreds. While Horohov's interest was on the effect of exercise on immune function, it was the differences between young and aged horses that caught his attention.

"What we noted was even before they were exercised, there were significant differences between the young horses and older horses in the ability of their immune systems to respond to stimulation," Horohov said. "So, that piqued my interest. We went on to publish a paper describing these differences. Prior to that paper, relatively little was known regarding immunosenescence (age-related changes in immune function) in horses."

In 1999, Horohov went to the Animal Health Trust in Newmarket, England, and expanded this earlier work. While in Newmarket, Horohov and his collaborators, Julie Kydd, MS, PhD, and Duncan Hanant, MS, PhD, vaccinated young and old horses and showed that the old horses did not respond as well to the vaccine as the young horses. This study provided evidence that age-related changes in older horses could affect their ability to respond to routine vaccination.

"One of the characteristics of immunosenescence in the elderly is their failure to respond to most vaccines; here we showed a similar defect in aged horses," Horohov explained.

When Horohov came to the University of Kentucky, he decided to revisit these earlier studies and to try and answer the question of why the immune system of aged horses is less responsive. Since recent research in human geriatric medicine had suggested that aging-related shortening of chromosomes might have a negative impact on immune function, his group turned their attention to this phenomenon in the horse.

One of Horohov's students at the time, Madhu Katapalli, worked with the Gluck Center's Teri Lear, PhD, to develop a method for evaluating the length of chromosomes in horses. Using this method, they were able to show that horses' chromosomes also shorten with age--the oldest horse they used (28 years) had significantly shorter chromosomes than those of the yearlings included in the study.

"One reason for doing that was to develop a means for determining the physiological age of a horse," Horohov explained. "While we are familiar with the concept of chronological age (age in years), not all individuals exhibit the same physiologically changes over time. Some of us exhibit signs of aging sooner than others. What we were looking for was a molecular marker for physiological aging, something you could use that would be easy to determine and would give us a consistent standard for comparing different horses."

When evaluating immune function in aged horses, Horohov's group noted that some of them had significant changes in their immune function, while a minority of the horses showed the responsiveness of a much younger horse.

"Again, why the difference?" Horohov said. "So, that's why we wanted to see if chromosome length was a better indicator of physiologic age and a better predictor of immunosenescence.

"What Madhu showed was that as horses aged, their chromosomes appeared to shorten," he said.

Chromosome length also correlated with immune function over the horse's lifespan, such that younger horses with longer chromosomes had better immune function than older horses with shorter chromosomes. However, chromosome length was not the final answer.

"Even though chromosome length was a good marker for the aging process overall, it wasn't the explanation as to why the changes in immune function were occurring," Horohov said. "Some of the aged horses with very short chromosomes still had signs of good immune function, and other old horses with relatively long chromosomes were clearly immunosenescent."

Horohov's lab continues to try and understand the basic mechanism for age-related changes in immune function.

"Not only does this relate to horses, but to anything that ages, including humans," Horohov said. "Age-associated changes in immune function are known to be associated with increased risk of infections and cancers. Anything we can do to increase the performance of the immune system in older individuals would have a direct effect on long term health and survival."

Jenny Blandford is the Gluck Equine Research Foundation Assistant at the Gluck Center. David Horohov, PhD, is the William Robert Mills Chair in Equine Immunology at the Gluck Center.

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